Diarrhea is one of the most common infectious diseases in the world. Although various viral, bacterial, and parasitic agents are suspected of causing acute infectious diarrhea and gastroenteritis, rotaviruses have been identified as the most important viral agent of diarrhea and gastroenteritis, e.g., in children and young animals in both developed and developing countries.
Rotaviruses cause 35–50% of severe diarrheal episodes in infants and young children in both developed and developing countries, and are the most important etiological agents of severe diarrhea in this age group. Rotaviruses are also the most important viral agents causing diahrrea in many animals, including swine units. Diarrhea caused by rotavirus is usually watery to pasty in consistency and may vary considerably in color. Affected pigs are usually depressed, off-feed, and dehydrated. Rotavirus destroys villi in the small intestine, hence, the clinical signs seen in diahrreal outbreaks. Additionally, rotaviruses have been linked with the occurrence of gasteroenteritis and the secondary infections by enteric bacteria in affected animals. That is, rotavirus infections are more difficult to treat when accompanied by secondary bacteria, thereby, enhancing the severity of the outbreak. Treatments for rotavirus are based on supportive treatment that addresses dehydration and starvation that occurs with a rotavirus infection. Treatments with antibiotics are only effective against secondary bacterial infections, and disadvantageous in that antibiotics may remain in the meat. Vaccination may be effective for the prevention of rotaviral infection, but may generate side effects.
Bacteria residing in the intestine may also cause diseases in the colonized host such as diarrhea in the intestines. A wide variety of microorganisms exist in the intestines of humans and animals, constituting intestinal microflora. They include bacteria that are not only beneficial to hosts, like lactic acid bacteria, but also some which are potentially or directly harmful to hosts, like E. coli, Salmonella, Staphylococcus, etc. Changes in the external environment, such as increased stress, infection of harmful microorganisms, and the like, may upset the normal balance of the intestinal microflora, resulting in the predominance of harmful microorganisms over beneficial ones. A shift in microflora can lead to abnormal health states of the host, such as diarrhea and, at the worst, even to death. When numbers of harmful microbes reach high levels in the intestine, the host is usually treated by the administration of antibiotics. Although they may be effective for the control of harmful microorganisms, antibiotics are not completely discharged from the host, but partially remain in the host's tissues. Additionally, extended administration of antibiotics induces antibiotic resistance in harmful microorganisms, making it finally impossible to effectively treat diseases they cause. Furthermore, recent legislation in response to environmental concerns stemming from food hygiene has been enacted to substantially lower the acceptable levels of antibiotics present in meats, milks and eggs of livestock. Hence, problems may occur upon use of antibiotics, let alone misuse or abuse thereof.
Thus, there is an urgent need to develop methods of treating and preventing infectious diarrhea caused by enteric viruses and microorganisms, and diahrrea associated with antibiotic theraphy.
There has been an increased interest for microbial species which can beneficially affect the microbial balance of the host, e.g. by producing antimicrobial components or by competitive growing.
Probiotics are a class of microorganisms that are defined as live microbial organisms that beneficially affect the animal and human hosts. The beneficial effects include improvement of the microbial balance of the intestinal microflora or by improving the properties of the indigenous microflora. A better understanding of probiotics in man and animals can be found in the following publication(Fuller R: Probiotics in Man and Animals, J Appl. Bacteriol 1989;66:365–378). Referring to the use of microorganisms in a positive way to benefit health, probiotics are prepared by formulating beneficial microorganisms that inhabit the intestine. Examples of microorganisms available for the preparation of probiotics include aerobes, anaerobes, lactic acid bacteria, and yeasts with lactic acid bacteria being the most popular. Probiotics enjoy the advantage of causing no side effects such as those resulting from the abuse of antibiotics, and inhibiting the abnormal proliferation of harmful microorganisms to maintain normal intestinal flora and to prevent the occurrence of illness. The known benefits of enteral administration of probiotic microorganisms include enhanced host defense to disease, improving colonization resistance of the harmful microflora and numerous other areas of health promotion. Probiotics have been suggested to play an important role in the formation or establishment of a well-balanced, indigenous, intestinal microflora in newborn children or adults receiving high doses of antibiotics.
For the prevention and treatment of diarrhea in livestock or poultry, live bacterial compositions have been developed for use as agents other than antibiotics. In live bacterial compositions, useful live bacteria are directly administered to livestock or poultry, where the bacteria are retained in the intestine of livestock or antagonize enterotoxic bacteria, e.g., Escherichia coli, to eliminate the enterotoxic bacteria, during passage of the live bacteria through the intestine. As a result, the enterobacteria microflora is improved so that diarrhea of livestock is prevented and treated. In addition, research results disclose that persistent administration of probiotics to livestock give rise to an increase in feed efficiency and weight gain.
For effective use, probiotics must be resistant to acid, particularly gastric and bile acid, in addition to having inhibitory activity against harmful microorganisms. Because probiotics are usually consumed in specially designed foods that are variously called nutraceuticals or functional foods, they experience acidic environments, first in gastric juice, a strong acid, and then in bile, until arrival at the intestine. In general, bacteria are killed or deactivated by gastric juice and bile acid. Therefore, probiotics must survive gastric juice and bile to reach the intestine, thereby exerting their beneficial functions.
Various kinds of lactic acid bacteria have been already disclosed as probiotics. Lactobacilli have been among the most studied species, and have in certain instances been shown to counteract the proliferation of pathogens. In fact, Lactobacillus therapy have increased in recent years with findings that probiotic Lactobacillus (a) improves the intersterial microflora, (b) prevents diarrhea, (c) affords protection from colon cancer for human populations, (d) reduces the incidence of experimentally induced large tumors in rats, (e) reduces the fecal concentraction of bacterial enzymes known to catalyze the conversion of procarcinogens to proximal carcinogens in humans, and (f) reduces the serum cholesterol levels in swine. In recent, a lactic acid bacterium, identified as Lactobacillus reuteri BSA-131, was reported to be tolerant of gastric and bile acids as well as inhibiting the proliferation of harmful microorganisms in the intestine (Chang, et al., Korean J. Appl. Microbiol. Biotechnol., 27, 23–27; Korean Pat. No. 10-211529-0000).